Methanol → N-(5-(5-amino-2-(3-methyl-1H-1,2,4-triazol-1-yl)phenoxy)pentan-2-yl)-2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

HRID 474288Notes

Reaction equation

HRID 474288 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:19][CH:20]([CH2:22][CH2:23][CH2:24][O:25][C:26]2[CH:31]=[C:30]([N+:32]([O-])=O)[CH:29]=[CH:28][C:27]=2[N:35]2[CH:39]=[N:38][C:37]([CH3:40])=[N:36]2)[CH3:21])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])[C:6]=2[N:7]=1.CO.C1COCC1.[Cl-].[NH4+]>[Fe].O>[NH2:32][C:30]1[CH:29]=[CH:28][C:27]([N:35]2[CH:39]=[N:38][C:37]([CH3:40])=[N:36]2)=[C:26]([CH:31]=1)[O:25][CH2:24][CH2:23][CH2:22][CH:20]([NH:19][C:4]1[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=3[F:18])[C:6]=2[N:7]=[C:2]([Cl:1])[N:3]=1)[CH3:21]

Participants

7

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 866681162-chloro-7-(2,4-difluorophenyl)-N-(5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine

Product 1

HCID 86668123N-(5-(5-amino-2-(3-methyl-1H-1,2,4-triazol-1-yl)phenoxy)pentan-2-yl)-2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amineYield 81.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

Iron powder-325 mesh (0.63 g, 11.4 mmol) was added to a round bottom flask charged with a mixture of 2-chloro-7-(2,4-difluorophenyl)-N-(5-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)pentan-2-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (0.65 g, 1.14 mmol), methanol (15 mL), THF (30 mL), water (15 mL) and ammonium chloride (0.61 g, 11.4 mmol). A water-cooled reflux condenser was attached to the flask and the heterogeneous mixture was heated at 70° C. with vigorous stirring for 2 h. The reaction mixture was filtered and washed with methanol. The filtrate was concentrated in vacuo. EtOAc (250 mL) was added to the residue and was washed with brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to afford the light yellow solid N-(5-(5-amino-2-(3-methyl-1H-1,2,4-triazol-1-yl)phenoxy)pentan-2-yl)-2-chloro-7-(2,4-difluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (500 mg, 81%). LC-MS (M+H)+=540.2. 1H NMR (400 MHz, CDCl3) δ ppm 8.32 (1H, s), 7.32-7.30 (1H, m), 6.96-6.94 (1H, m), 6.81-6.75 (2H, m), 6.34-6.29 (2H, m), 4.83 (1H, br m), 4.44-4.43 (2H, m), 4.09-4.00 (2H, m), 3.77 (2H, br s), 3.13-3.12 (1H, m), 2.64-2.56 (2H, m), 2.47 (3H, s), 1.94-1.80 (3H, m), 1.63-1.61 (2H, m), 1.27-1.22 (3H, m).

Workup

  1. temperaturereflux condenser
  2. filtrationThe reaction mixture was filtered
  3. washwashed with methanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. additionEtOAc (250 mL) was added to the residue
  6. washwas washed with brine
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-9a9be1591958401c8f8aeb448e0748ab
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Reaction notes

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